Dabigatran Bleeding Risk Stratified by Age in Atrial Fibrillation

A lower dose of dabigatran (110 mg twice daily) may mitigate the increased risk of extracranial bleeding in older patients.

Dabigatran, compared with warfarin, is associated with lower rates of stroke and intracranial bleeding across various age groups in patients with atrial fibrillation (AF), according to a study published in Heart1

The prevalence of AF and related stroke risk increase with age, highlighting the importance of identifying stroke prevention strategies in older patients with AF. Although vitamin K antagonists decrease the risk of stroke by roughly two-thirds vs placebo, previous findings show that clinicians may not prescribe such agents in elderly patients due to concerns about an increased bleeding risk.2-4

Noting these age-related differences, as well as those pertaining to drug metabolism and comorbid conditions, the investigators analyzed data from the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY; ClinicalTrials.gov identifier: NCT00262600) trial to examine the effects of dabigatran vs warfarin on rates of mortality, stroke, and bleeding according to age.

The sample in the RE-LY trial included 10,855 AF patients younger than age 75; 4231 age 75 to 79; 2305 age 80 to 84; and 722 age 85 or older. Patients were followed for up to 3 years.

The results of the RE-LY study had revealed that dabigatran 150 mg twice daily was superior to warfarin for the prevention of stroke or noncentral nervous system (non-CNS) systemic embolism, while dabigatran 110 mg twice daily was noninferior to warfarin for these outcomes. The findings further showed a reduction in intracranial bleeding with both doses of dabigatran.

The present analysis demonstrated lower rates of stroke with both doses of dabigatran vs warfarin. For the 150 mg dose, the hazard ratio (HR) ranged from 0.63 (95% CI, 0.46-0.86) in patients <75 years to 0.70 (95% CI, 0.31-1.57) in patients ≥85 years. For the 110 mg dose, the HR ranged from 0.52 (95% CI, 0.21-1.29) to 1.08 (95% CI, 0.73-1.60). In addition, less intracranial bleeding was observed with both dabigatran doses compared with warfarin. These benefits were consistent across all age groups.

Lower rates of extracranial major bleeding were also found for both doses of dabigatran vs warfarin in younger patients: HR, 0.78 (95% CI, 0.62-0.97) for 150 mg; and HR, 0.72 (95% CI, 0.57-0.90) for 110 mg. In patients age 80 or older, however, similar or higher rates were observed: HR, 1.50 (95% CI, 1.03-2.18) for 110 mg; and HR, 1.68 (95% CI, 1.18-2.41) for 150 mg.

“Both doses of dabigatran provide excellent protection against stroke and non-CNS systemic embolism and much lower rates of intracranial bleeding than warfarin, irrespective of age,” the researchers wrote. The increased risk of extracranial major bleeding in elderly patients “can be mitigated by reducing the dabigatran dose in elderly patients from dabigatran 150 mg twice daily to 110 mg twice daily.”